The objective of this career development award is to provide Dr. Mala Pande with the knowledge and experience necessary to become an independent genetic epidemiologist in the field of cancer prevention research, specializing in hereditary and familial cancers. This proposal builds upon her previous training as a cancer prevention scientist in colorectal cancer research, and outlines further training in breast cancer research, genetics and emerging analytic approaches for genetic analyses. The proposed research and training plan will allow Dr. Pande to develop content area knowledge, research methods skills and academic survival skills with the overarching goal of becoming an independent investigator. She will accomplish the goals of this proposal through a combination of coursework, workshops, seminars and mentored research. The coursework will be focused on enhancing her training in cancer biology, statistical genetics and advances in genome-wide association analyses. A highly qualified team of mentors and collaborators will supervise her training and guide her research to ensure that she meets her goals. The institution (MD Anderson Cancer Center) is committed to providing her with the protected time, space and resources necessary to achieve the goals of this career development award. The research component of this proposal involves examining susceptibility markers for a breast-colon cancer phenotype, which is characterized by co-occurrence of breast and colon cancer among individuals and families. Breast and colorectal cancer account for a significant cancer burden overall and are often seen to occur together in families with no known genetic predisposition or syndromes. Identifying these high risk families can provide a significant cancer prevention benefit. To achieve the goals of this research, the specific aims are: 1) To determine genetic susceptibility markers associated with the breast-colon cancer phenotype by examining genome-wide association study (GWAS) data; 2) To determine the association of epidemiologic risk factors with the breast-colon phenotype in the context of the underlying genetic risk profile; and 3) To ascertain possible functional variants in the regions containing loci associated with the disease phenotype. These specific aims will be accomplished using secondary data from the Breast and Colon Cancer Family Registries (CFRs) for which approvals are in place from both CFRs. The principal investigators of the parent breast cancer GWAS and colorectal cancer GWAS are consultants for her study and will share their expertise for her project. The proposed research will provide important knowledge regarding the genetic and non-genetic predictors of risk for this fairly common phenotype that is not well understood. In addition, these studies will provide the applicant with preliminary data to develop further hypothesis for understanding and addressing cancer risk in the breast-colon and multiple cancer predisposed individuals and families over the longer term. The cancer prevention goal of this research is the identification of individuals at high risk for cancer development for whom screening and early detection would be most beneficial in reducing the burden of cancer.